RhoA localization with caveolin-1 regulates vascular contractions to serotonin
| العنوان: | RhoA localization with caveolin-1 regulates vascular contractions to serotonin |
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| المؤلفون: | Kathryn G. Lamping, Sarah K. England, Daniel W. Nuno |
| المصدر: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 303:R959-R967 |
| بيانات النشر: | American Physiological Society, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, rho GTP-Binding Proteins, Serotonin, RHOA, Cardiovascular and Renal Integration, Physiology, Caveolin 1, Biology, Muscle, Smooth, Vascular, Calcium in biology, Mice, Membrane Microdomains, Physiology (medical), Caveolae, Animals, Rho-associated protein kinase, Lipid raft, Aorta, Mice, Knockout, rho-Associated Kinases, Arteries, Cell biology, Mice, Inbred C57BL, Biochemistry, Vasoconstriction, Models, Animal, biology.protein, rhoA GTP-Binding Protein, Vascular smooth muscle contraction, Muscle Contraction, Signal Transduction |
| الوصف: | Vascular smooth muscle contraction occurs following an initial response to an increase in intracellular calcium concentration and a sustained response following increases in the sensitivity of contractile proteins to calcium (calcium sensitization). This latter process is regulated by the rhoA/rho kinase pathway and activated by serotonin. In multiple cell types, signaling molecules compartmentalize within caveolae to regulate their activation. We hypothesized that serotonin differentially compartmentalizes rhoA within caveolar versus noncaveolar lipid rafts to regulate sustained vascular contractions. To test this hypothesis, we measured aortic contractions in response to serotonin in wild-type (WT) and cav-1-deficient mice (cav-1 KO). RhoA-dependent contractions in response to serotonin were markedly augmented in arteries from cav-1 KO mice despite a modest reduction in rhoA expression compared with WT. We found that under basal conditions, rhoA in WT arteries was primarily localized within high-density sucrose gradient fractions but temporally shifted to low-density fractions in response to serotonin. In contrast, rhoA in cav-1 KO arteries was primarily in low-density fractions and shifted to high-density fractions in a similar timeframe as that seen in WT mice. We conclude that localization of rhoA to caveolar versus noncaveolar lipid rafts differentially regulates its activation and contractions to rhoA-dependent agonists with greater activation associated with its localization to noncaveolar rafts. Disruption of rhoA localization within caveolae may contribute to increased activation and enhanced vascular contractions in cardiovascular disease. |
| تدمد: | 1522-1490 0363-6119 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b37df45665ad1371c1e72ca0ce08c0fb https://doi.org/10.1152/ajpregu.00667.2011 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b37df45665ad1371c1e72ca0ce08c0fb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221490 03636119 |
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